Distant regulatory genes which are not closely linked to the structural gene they regulate, and so presumably send diffusible molecular regulatory signals, are poorly understood in higher eukaryotes. Our goal in this project is to identify a set of such regulatory loci controlling alcohol dehydrogenase (ADH) expression in Drosophila and to characterize these for their location, tissue specificity of action, and molecular level of function. We would also like to test for possible interactions of the regulatory genes with each other and with the structural gene they regulate. These loci will be identified by dosage dependent effects on ADH expression in segmental aneuploidy experiments and by screening for natural variants of regulatory genes. This information should be useful in helping to define the organization of eukaryotic gene regulation and may have evolutionary implications as well. It should also provide a necessary beginning to asking questions about the molecular nature of the regulatory signals between genes in eukaryotes.